Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task

Eric J. Nunes; Patrick A. Randall; Alexavier Estrada; Brian Epling; Evan E. Hart; Christie A. Lee; Younis Baqi; Christa E. Müller; Mercè Correa; John D. Salamone

doi:10.1007/s00213-013-3285-4

Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task

Eric J. Nunes, Patrick A. Randall, Alexavier Estrada, Brian Epling, Evan E. Hart, Christie A. Lee, Younis Baqi, Christa E. Müller, Mercè Correa, John D. Salamone^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

Abstract

Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A_2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

Original language	English
Pages (from-to)	727-736
Number of pages	10
Journal	Psychopharmacology
Volume	231
Issue number	4
DOIs	https://doi.org/10.1007/s00213-013-3285-4
Publication status	Published - Feb 2014
Externally published	Yes

Keywords

Accumbens
Adenosine
Anergia
Depression
Fatigue
Motivation

ASJC Scopus subject areas

Pharmacology

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10.1007/s00213-013-3285-4

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Nunes, E. J., Randall, P. A., Estrada, A., Epling, B., Hart, E. E., Lee, C. A., Baqi, Y., Müller, C. E., Correa, M., & Salamone, J. D. (2014). Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology, 231(4), 727-736. https://doi.org/10.1007/s00213-013-3285-4

Nunes, EJ, Randall, PA, Estrada, A, Epling, B, Hart, EE, Lee, CA, Baqi, Y, Müller, CE, Correa, M & Salamone, JD 2014, 'Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task', Psychopharmacology, vol. 231, no. 4, pp. 727-736. https://doi.org/10.1007/s00213-013-3285-4

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title = "Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task",

abstract = "Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.",

keywords = "Accumbens, Adenosine, Anergia, Depression, Fatigue, Motivation",

author = "Nunes, {Eric J.} and Randall, {Patrick A.} and Alexavier Estrada and Brian Epling and Hart, {Evan E.} and Lee, {Christie A.} and Younis Baqi and M{\"u}ller, {Christa E.} and Merc{\`e} Correa and Salamone, {John D.}",

note = "Funding Information: Acknowledgments This work was supported by a grant to J.S. from the National Institute of Mental Health (MH094966), and to Merce Correa from Fundaci{\'o} Bancaixa/U. Jaume I. (P1.1B2010-43), and a SURF grant to B. Epling.",

year = "2014",

month = feb,

doi = "10.1007/s00213-013-3285-4",

language = "English",

volume = "231",

pages = "727--736",

journal = "Psychopharmacology",

issn = "0033-3158",

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number = "4",

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T1 - Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta

T2 - Studies with the concurrent fixed ratio 5/ chow feeding choice task

AU - Nunes, Eric J.

AU - Randall, Patrick A.

AU - Estrada, Alexavier

AU - Epling, Brian

AU - Hart, Evan E.

AU - Lee, Christie A.

AU - Baqi, Younis

AU - Müller, Christa E.

AU - Correa, Mercè

AU - Salamone, John D.

N1 - Funding Information: Acknowledgments This work was supported by a grant to J.S. from the National Institute of Mental Health (MH094966), and to Merce Correa from Fundació Bancaixa/U. Jaume I. (P1.1B2010-43), and a SURF grant to B. Epling.

PY - 2014/2

Y1 - 2014/2

N2 - Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

AB - Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

KW - Accumbens

KW - Adenosine

KW - Anergia

KW - Depression

KW - Fatigue

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Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task

Abstract

Keywords

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